For a pathogen to successfully transmit among hosts and become established in the population, it must ‘run the gauntlet’ of defences within individual hosts (Ewald, 1983; Handel & Rohani, 2015; van Baalen & Sabelis, 1995). Intuitively, the strong connections between within-host infection dynamics and transmission success make sense. Mathematical models and the few empirical studies (e.g. helminths, HIV, avian influenza, rodent malaria) that explicitly link within-host and between-host processes confirm this intuition (Coombs, Gilchrist, & Ball, 2007; Handel & Rohani, 2015; Mideo, Alizon, & Day, 2008; van Leeuwen, Budischak, Graham, & Cressler, 2019). Yet, while the importance of these cross-scale connections is widely acknowledged, for most infectious diseases our understanding of within-host dynamics remains limited—even for model organisms that are amenable to sophisticated and finely controlled laboratory experiments (Grant et al., 2008; Mideo, Day, & Read, 2008; Westwood et al., 2019). A quantitative understanding of within-host infection dynamics remains challenging for at least two key reasons. First, and most obvious, the logistical constraints associated with tracking pathogen dynamics that are concealed within a host hinders our understanding of the entire life history of disease, which typically proceeds in a step-wise fashion such that earlier steps influence later steps (Fenton, Antonovics, & Brockhurst, 2012; Hall, Bento, & Ebert, 2017). Second, how hosts respond to and cope with infection depends sensitively on the host's age (reviewed by: Ben-Ami, 2019). As hosts grow and develop, differences in body size govern energy acquisition and allocation, encounter rates with parasites and pathogens, susceptibility to infection, and immune responses. Host age can therefore influence all steps of infection from pathogen exposure and establishment to clearance and recovery (Ashby & Bruns, 2018; Hall, Sivars-Becker, Duffy, Tessier, & Caceres, 2007; Tate & Rudolf, 2012). Indeed, host age affects the manifestation and pathophysiology of plant (Ashby & Bruns, 2018; Develey-Rivière & Galiana, 2007; Sharabani et al., 2013), wildlife (Caraco et al., 2002; Dwyer, 1991; Hall et al., 2007) and human diseases (Carran, Ferrari, & Reluga, 2018; Keeling & Rohani, 2008). Such, age-specific processes within-hosts can scale up to fundamentally alter epidemiological dynamics as seen, for example, in recent outbreaks of measles (Cutts et al., 2020) and coronavirus disease (SARS-CoV-2; Wu et al., 2020). Therefore, an important objective for empirical studies is to follow the entire disease life history—across different stages of host ontogeny (Ben-Ami, 2019). Such information will help foster a more comprehensive and biologically realistic understanding of within-host interactions and how they influence population-level dynamics. In this issue of Functional Ecology, Izhar, Gilboa, and Ben-Ami (2020) examine how within-host infection dynamics vary in hosts that are infected at different ages. The authors focus on a model system, the zooplankton Daphnia magna and the castrating bacterial pathogen Pasteuria ramosa. Their results indicate that juvenile and adult Daphnia, like many hosts, differ in their susceptibility to pathogens, which subsequently affects host and pathogen fitness. By explicitly examining links between age at exposure, physiological mechanisms of defence, and pathogen traits over the entire infection cycle, the authors uncover novel mechanisms that govern age-specific patterns of virulence and transmission (i.e. disease life history: Day, 2003; Mideo et al., 2011). Because the zooplankton host is transparent, the authors were able to use a combination of compound and fluorescent microscopy techniques to collect high-resolution measurements of host physiology and pathogen developmental cycles over the entire course of infection (approximately 30–35 days). This detailed dissection of within-host infection dynamics at such a high degree of temporal resolution allowed the authors to quantify links between host age and key epidemiological parameters, such as the length of time it takes for the pathogen to establish an infection, the development and growth of pathogen life-history stages within hosts, and whether a host was able to clear the infection and recover. This sophisticated examination of within-host infection dynamics is rare and provides key insight into the physiological underpinnings of host defence. Traditionally, research on host defence has largely focused on immune functions. The emerging picture, however, indicates that host defence involves an arsenal comprised of immune cells, physiology, metabolism, gut microbes, and behavioural changes. For instance, in many organisms, oesophageal molting is an important part of defence and is particularly common in arthropods. This physiological mechanism is also a crucial component of defence for the focal host–pathogen system. In order to spread to other parts of the host's body cavity, the pathogen must encounter the host, activate and penetrate the cuticula in the host's oesophagus (Hall et al., 2017). Importantly, Izhar et al. (2020) were able to track the timing of molting events in the host, which sheds its exoskeleton, including its oesophagus, in order to grow. This work demonstrates that while juvenile (5-day-old, pre-reproductive) hosts molt earlier and more frequently (which could enhance their chances of escaping pathogen penetration), the pathogen is able to penetrate the oesophagus much more quickly in juveniles relative to adults. These differences may arise due to ontogenetic differences in the thickness or composition of the oesophageal cuticle. Regardless of the specific traits, this tension means that juvenile hosts are susceptible during three quarters of their molting cycles, whereas their adult counterparts are susceptible for only half of their molting cycles. The stronger physiological defence in adults resulted in fewer adults becoming infected in the first place. In adults that did become infected, pathogen development was delayed and typically did not progress beyond the first developmental cycle. In other words, adults were able to clear infections, reduce overall pathogen load (despite the larger host size) and prevent the pathogen from developing mature transmission stages. Thus, Izhar et al. (2020) provide compelling evidence that the timing of key processes within hosts alters how hosts and pathogens interact, affecting host recovery and pathogen load, all of which can scale up to shape between-host transmission. This study raises several important questions for evolutionary epidemiology more generally. For example, the authors' series of detailed experiments demonstrates that when hosts become infected as adults, they deploy both anti-infection and anti-growth mechanisms of resistance (Boots, Best, Miller, & White, 2009; Donnelly, White, & Boots, 2015; Gandon, Mackinnon, Nee, & Read, 2001). Theory predicts, and empirical studies show, that both anti-growth and anti-infection resistance can favour faster growing and more virulent pathogens that overcome these defences (de Roode, Fernandez de Castillejo, Faits, & Alizon, 2011). This system is ideal for testing these (and other) questions to better understand how host demography (age structure) and within-host infection dynamics scale up to alter host–pathogen (co)-evolution, with implications for both conservation and public health policies (Gandon et al., 2001; Mideo, Alizon, et al., 2008; van Leeuwen et al., 2019; Westwood et al., 2019). Clearly, we still have a long way to go in this endeavour but the study by Izhar et al. (2020) bring us closer to that goal.