We will then review some commonly suggested microglial targets and pathways, i.e., cluster of differentiation 33 (CD33), KCa3.1, kynurenines (KYN), ionotropic P2 receptor 7 (P2X7), programmed death-1 (PD-1), Toll-like receptors (TLRs), and triggering receptor expressed in myeloid cells 2 (TREM2), discussing their potential role in AD and their respective challenges in regard to drug discovery. This evidence concerns the gene TREM2 and Alzheimer disease.