Antibiotics are important secondary metabolites that produced through complex biosynthetic pathways by some microorganisms in specific conditions. They have been the best option for many infectious diseases in the past decades. Diversity of antibiotic groups makes them to be effective for a wide range of microbial infections. These valuable compounds are produced mostly by genus Streptomyces in specific conditions. Optimization of medium composition and fermentation process are of vital importance in pharmaceutical industries for increasing antibiotic production in large scale and minimization of operating costs. This review aims to communicate about different factors affecting on antibiotic synthesis in streptomycetes.