The discovery of biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles by Patrick Couvreur has opened large perspectives in nanomedicine. Nanoparticles made from different types of PACA monomers have been used in different applications such as the treatment of intracellular infections or the treatment of multidrug resistant hepatocarcinoma. This latest application led to a Phase 3 clinical trial of Livatag ® , a PACA nanoparticulate formulation of doxorubicin. Despite the success of PACA nanoparticles, the need to develop novel type of nanoparticles with higher drug loadings and lower burst release was tackled by the discovery of squalene-based nanoparticles where the drug is covalently linked to the lipid derivative and the resulting conjugate self-assemble into nanoparticles. This pioneering work was accompanied by a wide range of novel applications which mainly dealt with the management of unmet medical needs (e.g., pancreatic cancer, brain ischemia and spinal cord injury). The present Review Article covers the most important steps of the pioneering work of Patrick Couvreur by trying to shed light on his outstanding career that has been a source of inspiration for many decades.