Orphenadrine citrate, a monomethylated derivative of diphenhydramine, has been used as a muscle relaxant and as an analgesic both alone or as a constituent of combination products. Data on the efficacy of orphenadrine alone and in combination with paracetamol for painful conditions are evaluated in the present review. From the available animal data it is concluded that the antinociceptive effect of orphenadrine has been clearly demonstrated but data have also clearly indicated that it has muscle relaxant properties. Human placebo-controlled studies have shown some support for the view that orphenadrine on its own acts as a mild analgesic in painful conditions associated with muscle spasm. Although only a small number of well-controlled studies have been completed with the combination product of orphenadrine/paracetamol, each supports the view that the combination has superior efficacy over paracetamol alone. There is no doubt that the combination product is more efficacious than placebo.