This review summarizes traditional and recent nonconventional, bioinspired, methods for the aqueous synthesis of colloidal semiconductor quantum dots (QDs). The basic chemistry concepts are critically emphasized at the very beginning as these are strongly correlated with the selection of ligands and the optimal formation of aqueous QDs and their more sophisticated structures. The synergies of biomimetic and biosynthetic methods that can combine biospecific reactivity with the robust and strong optical responses of QDs have also resulted in new approaches to the synthesis of the nanoparticles themselves. A related new avenue is the recent extension of QD synthesis to form nanoparticles endowed with chiral optical properties. The optical characteristics of QD materials and their advanced forms such as core/shell heterostructures, alloys, and doped QDs are discussed: from the design considerations of optical band gap tuning, the control and reduction of the impact of surface traps, the consideration of charge carrier processes that affect emission and energy and charge transfer, to the impact and influence of lattice strain. We also describe the considerable progress in some selected QD applications such as in bioimaging and theranostics. The review concludes with future strategies and identification of key challenges that still need to be resolved in reaching very attractive, scalable, yet versatile aqueous syntheses that may widen the scope of commercial applications for semiconductor nanocrystals.