The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug-microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed.