Generally, most machine parts are loaded with a combination of different variable forces and moments. This often causes a state of multiaxial stress in the fatigue critical areas of the parts. In most cases, a nonproportional cyclic multiaxial state of stress occurs. Compared to the in-phase loading, a multiaxial loading with a phase difference of 90° between the stress components and a load ratio of γ a /∊ a = 1.33 (τ a /σ a ≈ 0.5) between tension/compression and torsion lead to a significant influence on the fatigue lifetime. The reason is the changing direction and ratio of the principal stresses during one cycle. The present research results for constant and variable amplitudes indicate that a phase difference of 90° causes a decreased lifetime compared with proportional loading under strain controlled tests with different ductile materials AlMgSi1 and SAE 1015, while the experimental analysis with magnesium die casting alloy AZ 91 reveals an increase of fatigue life compared with the in-phase loading. The lifetime prediction with a new concept on the basis of microcrack growth is compared with the experimental results.