Since Alexander Fleming discovered penicillin in 1982 fungi was used as a very important source of antibiotics and secondary metabolites due to their importance. Similar to higher plants and bacteria, fungi have the capacity to generate various secondary metabolites having biological effects, such as alkaloids, terpenoids and anthraquinones. The Ascomycete genus Chaetomium is a rich source of new and bioactive secondary metabolites, which are crucial compounds. A broad variety of biomolecules have been identified from genus Chaetomium as natural antioxidants, including nucleobases, polyketides, terpenoids, flavonoids, coumarins, xanthones, semiquinones, peptides, and phenolic acids. Other compounds belonging to diverse structural types of chaetoglobosins, epipolythiodioxopiperazines, azaphilones have been recorded. The majority of these Chaetomium's metabolites are characterized by antibiotic, anticancer, cytotoxic, antimalarial, enzyme inhibitory, and other medical and pharmaceutical activities. In this review we will focus on the chemistry of some important secondary metabolites produced by the genus Cheatomium and their biological uses.