Outbreeding depression lowers progeny fitness from crosses between genetically distant individuals. It opposes inbreeding depression but both can occur together. First mechanism disrupts local adaptation in F1 hybrids. Second mechanism breaks co-adapted gene complexes in F2 or later. Interspecific hybrids like mules show sterility and reduced fitness. Hybrid vigor in F1 can mask outbreeding depression. Plant breeders use F1 hybrids for vigor but avoid further breeding due to unpredictable low fitness. Outbreeding depression worsens without new co-adapted complexes. Large populations with selection can restore fitness over generations. Recovery requires hybrid persistence through initial fitness decline. Different mechanisms operate simultaneously but dominance varies by population. Extreme cases involve different orthologous genes. Recombination undermines positive epistasis in later generations. Limited outcrossing allows selection to forge new adaptations. Strong selection uses F1 diversity for environmental adaptation. Fitness can exceed parental levels post-recovery.