Granulocyte colony stimulating factor (G-CSF) is a naturally occurring potent neutrophil growth factor. Recombinant human G-CSF has been developed by pharmaceutical companies, and since the late 1980's, multiple clinical trials have explored its efficacy in a variety of medical conditions. These include various inherited and acquired neutropenia, as well as mobilization of hematopoietic stem cells and progenitors for transplantation. Interestingly, in several type of inherited neutropenia where no randomized controlled studies have ever been conducted, its chronic use is considered critical for survival and deemed a standard of care. Unfortunately, it the settings of cancer treatment-related neutropenia and post hematopoietic stem cell transplantation, controversy still prevails whether universal usage of drug is cost effective despite innumerous randomized clinical trials. This review will focus on the clinical applications of G-CSF in the setting of inherited and acquired bone marrow failure, cancer treatment-related neutropenia and hematopoietic stem cell transplantation.