Alkaloids are typically found in plants and certain animals, but are rare in actinomycetes. Recently, there have been significant advances in the discovery of bacterial alkaloids and the elucidation of their biosynthetic pathways. Based upon biosynthetic insights, a specialized class of secondary metabolites termed piperidine polyketide alkaloids (PPAs) has been identified from actinomycetes. PPAs exhibit very diverse structures with multiple heterocyclic moieties, i.e., piperidine, pyridine, cyclopenta[b]piperidine, indolizidine, and quinolizidine. However, these alkaloids are derived from similar biosynthetic intermediates that share a common structural feature of a piperidine nucleus linked to a polyene chain. PPAs have the skeletons biosynthesized via the polyketide pathway, and the piperidine nucleus formed by a conserved thioester reduction-transamination process. Alkaloids are usually classified in terms of their heterocyclic skeletons. This review highlights new insights into the classification of PPAs from the perspective of integrated biosynthesis and structures. The natural occurrence, structure elucidation, biological activity, and biosynthesis of PPAs are comprehensively summarized.