Weak grip strength is a key component of sarcopenia and frailty and is associated with subsequent poor health, disability and mortality. The measurement could be useful as a biomarker of overall strength, immobilization and quality of life with superiority over chronological age. Although stand-alone measures of handgrip strength provide robust health information, the clinical meaningfulness to determine prevention and treatment options for weakness remains limited because the etiology of muscle weakness remains unclear. Therefore, disentangling how handgrip strength is associated with health conditions that are metabolically or neurologically driven may improve our understanding of the factors linked to handgrip strength. The purpose of this topical review is to highlight and summarize evidence examining the associations of handgrip strength with certain health outcomes that are metabolically and neurologically driven. From this perusal of the literature, we posit that stand-alone handgrip strength could be considered as an umbrella assessment of the body systems that contribute to strength capacity. Recommendations for future strength capacity-related research are also provided. Physical well-being and in particular muscle strength, estimated by grip strength, may increase health-related quality of life and are therefore an important source for well-being during old age.