The first biological tumor necrosis factor (TNF)-α inhibitor to be approved for dermatological use is etanercept. Etanercept is a fusion protein that consists of the extracellular portion of the TNF-α receptor linked to the Fc portion of human immunoglobulin G. By binding to soluble and cell membrane-bound TNF-α, it has been shown to be effective in the treatment of many TNF-mediated inflammatory diseases. In the USA, etanercept has been approved by the FDA for use in rheumatoid arthritis (since 1998), psoriatic arthritis (since 2002), ankylosing spondylitis (since 2003), psoriasis (since 2004) and juvenile rheumatoid arthritis (since 2000). The use of etanercept as an approved and off-label therapeutic in dermatology is evaluated in this review. The safety issues related to the use of etanercept will also be reviewed.