Frailty is a dynamic and multidimensional clinical condition characterized by the depletion of system reserves, resulting in a loss of redundancy and increased vulnerability to any stressful event. This loss of resilience implies not only a poorer and more difficult recovery from baseline homeostasis but a disproportionate increase in harmful health outcomes from even minor insults. There are two models of frailty that have received the most attention within the community: the frailty phenotype and the frailty index. Frailty and comorbidity represent two distinct, but related, clinical concepts. The term comorbidity designates the co-occurrence of different noncommunicable diseases (NCDs) in the same individual. Comorbidity, however, does not only represent the sum of different NCDs, but a clinical condition in itself. In fact, it is conceived as a synergy of the different NCDs associated with worse health outcomes and a more complex clinical management than the simple sum of the individual NCDs. Evidence supports the role of frailty and comorbidity as mutual risk factors. Women have been found to acquire slightly more general comorbidities than men, but paradoxically enjoy a longer life expectancy. Women also experience poorer health which has, at least in part, been attributed to psychosocial differences. It is unclear why women live longer despite suffering higher levels of frailty. This may be due to the distinctive profile of NCDs, which may not be life-threatening in women, a lower physiological reserve in men, or other reasons.