Biopharmaceuticals were copies of endogenous human proteins developed in the mid-1990s that were characterized by complex three-dimensional, high-molecular weight compounds. What made them unique was that contrary to classical chemotherapeutical drugs, they were manufactured by living cells. One of these biopharmaceuticals was granulocyte-colony stimulating factor (G-CSF). Once their patent expired, generic versions appeared in pharmacies. They are now called biosimilars. There are several biosimilar G-CSFs approved in Europe: Biograstim®/Filgrastim ratiopharm/Ratiograstim®/Tevagrastim® (XM02); Zarzio® and Nivestim®. All these new products are manufactured in facilities with state-of-the-art technology. All products have passed the regulatory requirements for approval, mainly phase I and phase III, with the consequent PD/PK evaluations and studies on efficacy and safety. However, there are still some concerns regarding their long-term evaluation, in particular, the limited experience at the time of approval of these products in terms of efficacy, safety and immunogenicity. For this reason, pharmacovigilance should be rigorous. A lot of work remains to be done in terms of clarification with regard to substituting a biosimilar G-CSF for the innovator product and, finally, information must be provided to physicians, pharmacists and patients to allow for proper decision-making. Ultimately, only clinical trials and effective post-marketing pharmacovigilance will provide definitive evidence that a biosimilar is comparable to the originator-reference product in terms of efficacy and safety.