Myeloid malignancies are a manifestation of clonal expansion of hematopoietic cells driven by somatic genetic alterations that may arise in a potential background of deleterious germline variants. As next-generation sequencing technology has become more accessible, real-world experience has allowed integration of molecular genomic data with morphology, immunophenotype, and conventional cytogenetics to refine our understanding of myeloid malignancies. This has prompted revisions in the classification and the prognostication schema of myeloid malignancies and germline predisposition to hematologic malignancies. This review provides an overview of significant changes in the recently published classifications of AML and myelodysplastic syndrome, emerging prognostic scoring, and the role of germline deleterious variants in predisposing to MDS and AML.