Virus particles are vehicles for transmission of the viral genetic information between infected and uninfected cells and organisms. They have evolved to self-assemble, to serve as a protective shell for the viral genome during transfer, and to disassemble when entering a target cell. Disassembly during entry is a complex, multi-step process typically termed uncoating. Uncoating is triggered by multiple host-cell interactions. During cell entry, these interactions occur sequentially in different cellular compartments that the viruses pass through on their way to the site of replication. Here, we highlight the general principles of uncoating for two structurally related virus families, the polyoma- and papillomaviruses. Recent research indicates the use of different compartments and cellular interactions for uncoating despite their structural similarity.