The effects of estrogen on tissues such as bone, endometrium and breast have been extensively studied, and the pleitropic effects of the female sex hormone are well established. Cartilage is not generally viewed as an estrogen responsive tissue. However, several epidemiological studies, and a few recent intervention studies supports that estrogen may have a role in osteoarthritis (OA), and recent animal studies further suggests that estrogen may be involved in regulation of cartilage turnover. Accordingly the issue of chondroprotrective properties of estrogen has received increased attention in recent scientific publications. In this review, we summarize current studies indicating a role for estrogen in the regulation of cartilage turnover and development of joint diseases. We report results from in vitro and animal studies where the effects of ovariectomy and treatment with estrogen and selective estrogen receptor modulators (SERM) on cartilage erosion have been evaluated. Furthermore, we report results from assessment of the effects of estrogen and SERM in postmenopausal women which shed new light on the interactions between estrogen and joint tissues. It still remains to be established whether estrogen or SERM could find a role in prophylaxis and/or treatment of OA, and much work lies ahead. Current data reviewed in this manuscript can be considered encouraging and they raise the hope that new treatment options for OA may become available based on estrogen and, in particular, compounds acting through the estrogen receptor. However, at present hormone replacement therapy and SERMs available in clinical practice, cannot be recommended as a therapy for arthritic disease.