Drug repurposing involves finding new indications for existing drugs or potential drug candidates. Drugs or candidates include those in clinical development with relevance to multiple diseases, drugs that have failed to demonstrate efficacy for a particular indication during clinical trials but have no major safety concerns, discontinued drugs, drugs not yet fully pursued and drugs for which patents are set to expire [1]. Opportunities for drug repositioning can arise from indirect observation as well as purposeful collaboration including physician and patient engagement. The focus of this editorial is primarily on the engagement of patients directly or through patient information to support drug repurposing endeavors. Engagement must permit the transition of patients from the role of simple participant to the mid-level informative role, and at the highest level of engagement the collaborative role. Table 1 outlines a newly devised continuum of patient engagement. The focus is on the engagement of the ‘lead patient’ [2]. ‘Lead patients’ – namely those patients that: are proactive with respect to their health, disease and treatment options, can provide a nuanced perspective to drug discovery, including through repurposing endeavors [2]. Specifically, patients can be a source of direct information with respect to off-label drug usage, patient records and patient communities can indirectly reveal drug repurposing opportunities, and patients can jointly collaborate in the search for new drug repurposing opportunities through the deciphering of information on drug pharmacology – system or – gene interaction or other design opportunities [3]. The engagement could not be more salient than for rare disease drug repurposing [4].