Topical diclofenac solution (Pennsaid) is a liquid formulation containing the NSAID diclofenac sodium (1.5% w/w). The solution base contains 45% w/w dimethyl sulfoxide (DMSO) to enhance the absorption of diclofenac through the skin. Topical diclofenac solution is applied directly to the knee for treatment of symptoms associated with osteoarthritis of the knee. In well designed 4- to 12-week trials in patients with primary osteoarthritis of the knee, topical diclofenac solution (40 drops four times daily) was significantly more effective than placebo or vehicle control (carrier solution without diclofenac) for improving Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain and physical function, and improving patient global assessment (PGA) and/or patient overall health assessment scores from baseline to the final assessments. Topical diclofenac solution (50 drops three times daily) was as effective as oral diclofenac 150 mg/day for improving WOMAC pain and physical function and PGA scores in a 12-week double-blind study in patients with osteoarthritis of the knee. Topical diclofenac solution was generally well tolerated. The most common treatment-emergent adverse event experienced by topical diclofenac solution recipients was dry skin at the application site. Gastrointestinal adverse events and abnormal laboratory parameters were less common with topical diclofenac solution than with oral diclofenac.