Poliovirus is the most extensively studied member of the order Picornavirales, which contains numerous medical, veterinary and agricultural pathogens. The picornavirus genome encodes a single polyprotein that is divided into three regions: P1, P2 and P3. P3 proteins are known to participate more directly in genome replication, for example by containing the viral RNA-dependent RNA polymerase (RdRp or 3Dpol), among several other proteins and enzymes. We will review recent data that provide new insight into the structure, function and mechanism of P3 proteins and their complexes, which are required for initiation of genome replication. Replication of poliovirus genomes occurs within macromolecular complexes, containing viral RNA, viral proteins and host-cell membranes, collectively referred to as replication complexes. P2 proteins clearly contribute to interactions with the host cell that are required for virus multiplication, including formation of replication complexes. We will discuss recent data that suggest a role for P3 proteins in formation of replication complexes. Among the least understood steps of the poliovirus lifecycle is encapsidation of genomic RNA. We will also describe data that suggest a role for P3 proteins in this step.