Neutropenia, and most notably febrile neutropenia, represents a significant complication following chemotherapy administration. Present agents used for the treatment of neutropenia include G-CSF, GM-CSF and G-CSF conjugated to polyethylene glycol (PEG) as pegylated G-CSF. Despite the availability and considerable efficacy of the above approved agents in reducing the risk of neutropenia and its complications remain significant issues in oncology. This article explores some of the biology behind the colony-stimulating factors and the recent advances in agents for the treatment and prevention of neutropenia, including the development of additional G-CSF agonists, chemoprotectants, retinoic receptor agonists and CXC chemokine receptor 4 antagonists.