Tunneling nanotubes (TNTs) are cellular connections, which represent a novel route for cell-to-cell communication. Strong evidence points to a role for TNTs in the intercellular transfer of signals, molecules, organelles, and pathogens, involving them in many cellular functions. In myeloid cells (e.g., monocytes/macrophages, dendritic cells, and osteoclasts), intercellular communication via TNT contributes to their differentiation and immune functions, by favoring material and pathogen transfer, as well as cell fusion. This chapter addresses the complexity of the definition and characterization of TNTs in myeloid cells, the different processes involved in their formation, their existence in vivo, and finally their function(s) in health and infectious diseases, with the example of HIV-1 infection.