Bacteria of the genus Nocardia are opportunistic pathogens that can cause a variety of infections in susceptible individuals. As members of the Actinomycete family, they are closely related to their powerhouse specialised metabolite-producing cousins, the Streptomycetes. Yet, the Nocardia have been underexplored compared to Streptomyces and represent an relatively untapped resource for natural product discovery. Here, we describe our experiences exploring the antimicrobial activity of a diverse culture collection of 200 human pathogenic Nocardia isolates held by our state microbiology reference laboratory. We show that organisms from this collection produce compounds capable of inhibiting the growth of the hospital superbugs MRSA and VRE. To investigate the genetics behind the production of these antibiotics, we have sequenced the genomes of these 200 isolates (including reference quality genomes of 70 isolates), which has provided further information on the immense secondary metabolic potential of these organisms. Our efforts have uncovered previously hidden biosynthetic pathways for these molecules and using a heterologous expression strategy, we have cloned and expressed several large gene clusters for the biosynthesis of predicted antibiotics,. Our investigation of this collection of strains, via a combination of molecular biology, genomics and chemical biology, provides new insights into this genus and their potential for specialised metabolite production.