Effective clinical practice is predicated on valid and relevant clinical science - a commodity in increasingly short supply. The pre-eminent place of clinical research has become tainted by methodological shortcomings, commercial influences and neglect of the needs of patients and clinicians. Researchers need to be more proactive in evaluating clinical interventions in terms of patient-important benefit, wide applicability and comparative effectiveness, and in adopting study designs and reporting standards that ensure accurate and transparent research outputs. Funders of research need to be more supportive of applied clinical research that rigorously evaluates effectiveness of new treatments and synthesises existing knowledge into clinically useful systematic reviews. Several strategies for improving the state of the science are possible but their implementation requires collective action of all those undertaking and reporting clinical research.