While polypathology and polypharmacy are well known risk factors for adverse drug reactions (ADRs), the association between geriatric conditions (GCs), i.e. a set of clinical and functional problems partly constitutive of and partly related to frailty, and ADRs is suspected but has not been fully elucidated. Several studies have assessed the relationship between single GCs and ADRs, but only a few studies have systematically evaluated the relationship between the whole spectrum of GCs and ADRs. The mechanism by which select GCs increase the risk of developing ADRs during a hospital stay might simply reflect a sort of general predictability of physical disability with respect to adverse outcomes. However, GCs pertaining to the physical dimension of frailty are generally associated with relevant changes in pharmacokinetics and pharmacodynamics of select drugs. While current evidence could not be considered either unequivocal or conclusive, select GCs, e.g. a history of falls and loss of independence in the activities of daily living, seem to define a condition of particular vulnerability of elderly patients to ADRs.