Advances in atom transfer radical polymerization (ATRP) are usually focused on reducing the metal catalyst concentration, using low toxicity metals or even metal-free catalysts, to minimize or avoid the contamination of polymers. In this work, the less toxic and inexpensive CuSO₄·5H₂O was used to replace CuBr₂, the most employed metal source for ATRP, to control polymerizations under homogeneous conditions. Well-defined (Đ ≤ 1.3) hydrophobic homopolymers of poly(methyl acrylate) (PMA), poly(methyl methacrylate) (PMMA), polystyrene (PS) and poly(butyl acrylate) (PBA) were obtained in various organic solvent/water mixtures with similar control as when CuBr₂ was used. The main limitation is the lower solubility of the CuSO₄/L complex in pure organic solvents compared with CuBr₂/L. The preparation of several hydrophilic polymers, namely poly(2-hydroxyethyl acrylate) (PHEA), poly((3-acrylamidopropyl)trimethylammonium chloride) (PAMPTMA), poly(2-hydroxyethyl acrylamide) (PHEAA), polyacrylamide (PAAm), poly(N,N-dimethylacrylamide) (PDMAA), poly(2-aminoethyl methacrylate hydrochloride) (PAMA), poly[oligo(ethylene oxide) methyl ether acrylate] (POEOA) and biorelevant block copolymers (PHEA-b-PAMPTMA and PAMPTMA-b-PHEAA) was successfully carried out in aqueous medium using different ATRP techniques. Future studies on this system will include the use of CuSO₄/L complexes in several organic solvents and in heterogeneous ATRP.