Diclofenac is a nonselective NSAID that, in its oral form, has been used for decades in the treatment of osteoarthritis. More recently, topical formulations have been developed to decrease the significant systemic exposure associated with oral diclofenac. Several formulations of both oral and topical diclofenac are now approved for the treatment of osteoarthritis in the USA and Europe. Although diclofenac has generally been shown to be relatively safe, some significant safety risks have been observed. For instance, oral diclofenac displays the classic gastrointestinal and cardiovascular effects of the NSAID class; however, topical formulations of the drug show a reduced incidence of these effects. Diclofenac is, thus, well established as an effective and relatively safe option for the treatment for osteoarthritis.