Fractographic studies on Al alloys and a nickel-base super-alloy point to the combined action of three major load-interaction mechanisms in controlling crack growth under variable-amplitude loading. These are crack closure, residual stress, and crack front incompatibility. Crack front incompatibility attenuates crack tip response to applied load and can also increase crack closure stress. Notch root residual stress affects crack closure, while crack tip residual stress moderates environment-enhanced fatigue crack extension. The latter effect disappears in vacuum. Experiments designed to isolate the effect of individual mechanisms provide a framework to model their synergistic action, consistent with microscopic observations of crack growth bands in variable amplitude fatigue.