The advancement in molecular technologies has given a breakthrough to explore the untapped and novel microbial isolates for characterization in every aspect as we can consider microbes as an important primary natural store house for key secondary metabolites and enzymes. Actinomycetes are the most fruitful source of microorganisms for all types of bioactive secondary metabolites, including agroactive-antibiotic molecules that are best recognized and most valuable for their role in agriculture and industries. In agriculture, actinomycetes are used as biocontrol agents against some pests and pathogenic organisms as well as plant growth-promoting (PGP) agents for crops. Use of different molecular methods, e.g., metagenomics, metatranscriptomics, genetic fingerprinting, proteogenomics, and metaproteomics, are more significant for classifying and discovering the immense diversity in microbial population and for understanding their interactions with other abiotic and biotic environmental elements. The opportunity of accessing inexpensive sequencing techniques has led to the assemblies of copious genomic data for actinomycetes, such as Streptomyces and related species, with the goal of discovering novel bioactive metabolic and their utility as PGP; however, the use of actinomycetes in agriculture using genomic approaches is in its initial stages.