Verticillium dahliae and related species are important plant pathogenic ascomycete filamentous fungi, which are causing severe plant diseases worldwide in a broad range of host plants. Their persistence in the soil is primarily mediated by melanized resting structures called microsclerotia, enabling long-term survival under different environmental conditions. This chapter provides an overview of Verticillium species infection strategies and survival mechanisms with a focus on the genetic regulation, which are required for causing pathogenicity. Favorable conditions trigger microsclerotia germination and growth towards the host plants. Specialized structures like hyphopodia promote the fungal penetration of plant roots. The pathogen grows towards and enters the vascular system, where it systemically spreads with the additional help of asexual conidia formation. Key regulatory networks for pathogenesis have been identified by various genetics screens and include the transcription factors Som1 and the Verticillium transcription activators of adhesion Vta2 and Vta3, which are connected to the MAPK cascades, and the unfolded protein response. They coordinate fungal development, host colonization, and stress adaptation and finally result in the disease phenotype. Melanin biosynthesis and oxylipin production are fungal secondary metabolism pathways, which play a critical role in both environmental persistence and virulence. Microsclerotia formation is tightly linked to developmental and environmental signals, involving a cascade of transcriptional regulators such as Sfl1, Vta1–3, and members of the velvet protein family. In total, V. dahliae survives for decades through melanized microsclerotia and orchestrates a genetically regulated infection strategy to silently invade, colonize, and lead to devastating crop diseases in a wide range of host plants, making its understanding important for identifying potential targets for sustainable disease control.