Rituximab is currently licenced for the treatment of CD20 positive lymphoma and rheumatoid arthritis (RA), however, it is increasingly being used off-label in a wide variety of non-haematological conditions. Although there are limited numbers of randomised controlled trials, there is a growing body of evidence for its efficacy in rheumatology, renal disease, solid organ transplantation, neuromuscular disorders, skin and endocrine disorders. The mechanism of action of rituximab in these conditions is not always clear and is likely to be via modification of both B and T cell function. Rituximab appears to be well tolerated in most groups of patients but certain side effects may be more prominent in particular conditions. This review examines the evidence base behind the use of rituximab in non-haematological conditions in adults and any special considerations that need to be taken into account when treating particular disease groups.