The two main protein degradation systems of eukaryotic cells, the ubiquitin-proteasome system and autophagy, have been thought of as quite separate systems. However, recent findings strongly suggest that there is crosstalk and even cooperation between these two degradation pathways. Ubiquitination and degradation of misfolded proteins by the ubiquitin-proteasome system have been investigated for some time, but much less is known about autophagic degradation of misfolded proteins. We will here discuss recent findings that shed some light on the cellular processes deciding when and how misfolded proteins are specifically selected for autophagic degradation in favor of proteasomal degradation.