Primary immunodeficiencies (PIDs) primarily affecting the phagocytes (neutrophils and macrophages) typically predispose patients to infections. However, one of the most clinically important features of these disorders is their relatively narrow spectrum of disease-specific infections. Invasive aspergillosis in the absence of immune suppression is essentially seen only in chronic granulomatous disease; disseminated nontuberculous mycobacterial infection in the absence of immune suppression is seen predominantly in patients with defects of the IFN-γ/IL-12 axis. In contrast, infections that are relatively common in some of the PIDs affecting the lymphoid system (Pneumocystis jiroveci and Streptococcus pneumoniae) are extremely uncommon in PIDs affecting phagocytes. Therefore careful attention to the microbiology laboratory early in the course of evaluation of a patient with recurrent infections and suspected of having a PID will help steer the workup in the appropriate direction. Over the last few years, there have been major advances in the molecular and cellular understandings of PIDs affecting phagocytes. As the field of PIDs becomes broader and more clinical and molecular definition becomes available, it is increasingly important to be able to identify likely pathways for investigation early in the evaluation. Here we have updated some of the more rapidly evolving aspects of PIDs affecting phagocytes, with a special emphasis on the associated microbiology.