Fatigue crack growth is a random process and various uncertainties affect the remaining useful life of engineering materials and structures. A general probabilistic life prediction methodology for accurate and efficient fatigue prognosis is proposed in this paper. The proposed methodology is based-on an inverse first-order reliability method (FORM) to evaluate the fatigue life at an arbitrary reliability level. An efficient searching algorithm for fatigue life prediction is developed and a numerical example is demonstrated. The prediction results are compared with direct Monte Carlo simulation for validation. Various experimental data are collected for model validation. Very good agreements are observed between model predictions and experimental data.