Production of fuels, therapeutic drugs, chemicals, and biomaterials using sustainable biological processes have received renewed attention due to increasing environmental concerns. Despite having high industrial output, most of the current chemical processes are associated with environmentally undesirable by-products which escalate the cost of downstream processing. Compared to chemical processes, whole cell biocatalysts offer several advantages including high selectivity, catalytic efficiency, milder operational conditions and low impact on the environment, making this approach the current choice for synthesis and manufacturing of different industrial products. In this review, we present the application of whole cell actinobacteria for the synthesis of biologically active compounds, biofuel production and conversion of harmful compounds to less toxic by-products. Actinobacteria alone are responsible for the production of nearly half of the documented biologically active metabolites and many enzymes; with the involvement of various species of whole cell actinobacteria such as Rhodococcus, Streptomyces, Nocardia and Corynebacterium for the production of useful industrial commodities.