Book excerpt: Although cancer development and progression depend on stochastic mutational events, the tumor has to be seen in the context of the host environment, and unraveling the environmental factors that support solid tumors is at the root of cancer prevention and cure. This Special Issue, focused on the dynamic crosstalk that occurs between tumor cells and the surrounding microenvironment and also including the cancer cells that represent a reservoir of self-sustaining cells for tumor maintenance, adds new knowledge about tumor–host interactions that is useful for novel diagnostic and therapeutic approaches.