Parainfluenza virus 5 (PIV5), known as canine parainfluenza virus in the veterinary field, is a negative-sense, nonsegmented, single-stranded RNA virus belonging to the Paramyxoviridae family. Parainfluenza virus 5 is an excellent viral vector and has been used as a live vaccine for kennel cough for many years in dogs without any safety concern. It can grow to high titers in many cell types, and its genome is stable even in the presence of foreign gene insertions. So far, PIV5 has been used to develop vaccines against influenza virus, respiratory syncytial virus, rabies virus, and Mycobacterium tuberculosis, demonstrating its ability to elicit robust and protective immune responses in preclinical animal models. Parainfluenza virus 5–based vaccines can be administered intranasally, intramuscularly, or orally. Interestingly, prior exposure of PIV5 does not prevent a PIV5-vectored vaccine from generating robust immunity, indicating that the vector can be used more than once. Here, these encouraging results are reviewed together along with discussion of the desirable advantages of the PIV5 vaccine vector to aid future vaccine design and to accelerate progression of PIV5-based vaccines into clinical trials.