Because the number of transplants is still fewer than the number of patients waiting for a donor organ, new concepts of therapy are needed that allow patients to bridge the time gap until heart transplantation or even to improve symptoms while on treatment. Ca(2+)-sensitisers are agents that directly influence myofilaments and/or the cross-bridge-cycle. Depending on the molecular mechanisms underlying their action, Ca(2+)-sensitisers have been divided into three classes. While, a number of Ca(2+)-sensitising drugs have been described, currently only the Ca(2+)-sensitisers pimobendan and levosimendan are in clinical use. This review provides a survey on the molecular mechanisms and the therapeutic effectiveness of Ca(2+)-sensitisers for the treatment of human heart failure.