D-penicillamine (D-pen) has gained wide-spread use as a potent suppressor of disease activity in rheumatoid arthritis (RA) and juvenile chronic arthritis (JCA). The drug has been established for antirheumatoid therapy on the basis of a considerable number of comparative clinical studies of D-pen treatment versus placebo or other disease modifying antirheumatic drugs (DMARDs). Despite the positive outcome of these trials, no comprehensive understanding of its mode of action has emerged. Development of more differentiated drug strategies, construction of combination treatment protocols and generation of agents with defined target specificities may imply a more favourable beneft to risk ratio in the management of RA.