Virus-like particles (VLPs) are protein-based, nanoscale, self-assembling, cage architectures, which have relevant applications in biomedicine. They can be used for the development of vaccines, imaging approaches, drug and gene therapy delivery systems, and in vitro diagnostic methods. Today, three relevant viruses are targeted using VLP-based recombinant vaccines. VLP-based drug delivery, nanoreactors for therapy, and imaging systems are approaches under development with promising outcomes. Several VLP-based vaccines are under clinical evaluation. Herein, an updated view on the VLP-based biomedical applications is provided; advanced methods for the production, functionalization, and drug loading of VLPs are described, and perspectives for the field are identified.