Frailty is a multidimensional syndrome, involving functional, nutritional, biological and psychological aspects. This condition, defined as a decreased resistance to internal and external stressors, is predictive of adverse health outcomes, including disability and mortality. Importantly, the frailty syndrome is usually considered a reversible condition, thus amenable of specific preventive interventions. Persistent pain in older adults is very common and has multiple determinants. This symptom represents a determinant of accelerated aging. In the present paper, we discuss available evidence examining the association between these two conditions. Despite the high prevalence of these two conditions and their shared underlying mechanisms, our search only retrieved few relevant studies. Most of them reported a relationship between pain (or analgesics consumption) and different operational definitions of frailty. Pain may represent a relevant risk factor as well as a potential target for interventions against the frailty syndrome, but further studies are needed.