This invention relates to long-acting injectable compositions for combating parasites in animals, comprising at least one isoxazoline active agent, a liquid PEG and/or a neutral oil, optionally a co-solvent, and optionally a pharmaceutically acceptable additive or excipient. This invention also provides new isoxazoline active agents with long-lasting efficacy against ectoparasites. The invention also provides for improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the novel isoxazoline compounds and long-acting injectable compositions of the invention to the animal in need thereof.