Mimicking the structure of natural proteins by recombinant biopolymers is a useful approach for the development of novel bioactive biomaterials with desired properties, that help elucidate molecular interactions in biological systems and elaborate strategies for tissue engineering and drug delivery purposes. Structurally based on elastin repeated motifs, recombinant human elastin-like polypeptides (HELPs) represent excellent examples of bio-inspired polymers proposed for tissue engineering, and recently exploited also for drug delivery applications. This Editorial reports on the latest advances in the research on HELP biopolymers for drug delivery and targeting applications. The main findings will be summarized with emphasis on the 'smart' properties of HELPs, which render this class of biopolymers particularly interesting in the whole biomedicine field. Considerations about further improvements of the current HELP-based systems will be provided, and a demonstration of the huge potential of HELPs in becoming leading material for drug delivery will be attempted.