Abstract: On-line determination of residual water content and sublimation end-point during freeze-drying is important and difficult. The control methods usually used such as theoretical model method, response method of product temperature, pressure rising method, moisture sensing method, residual gas analysis method, proton nuclear magnetic resonance and weight sensing method are explained. The superiority of NMR method and moisture sensing method are explained. The superiority of NMR method and moisture sensing method will develop a new outlet for experimental and theoretical research of freeze-drying.