Centrosome serves as the primary site of microtubule organization in a majority of animal cells. These microtubules carry out several significant functions in the cell such as cell division, chromosome segregation, mechanical support and cellular transport. Proteins localized at the centrosome play extensive role in orchestrating the process of microtubule organization, growth and stabilization in space and time. Anomalies in centrosome number, structure and functioning disturb microtubule organization and lead to several human diseases. Advancements in proteomics and microscopy methods have been instrumental in identifying molecular mechanisms pertaining to the microtubule organizing function of centrosomes. This review focuses on the involvement of centrosome as a microtubule nucleating center of the cell. We present the major molecular mechanisms at the centrosome which affect microtubule nucleation and activation. Finally, we discuss human diseases associated with defective microtubule organization resulting from centrosome abnormalities. © 2021, Indian Institute of Science.