IR can detect the local environment of the lipid interface by probing the frequency fluctuations of lipid ester carbonyl groups, where the lineshape and dynamics of 2D IR spectra are correlated with the water network at the interface. However, direct detection of the interfacial environment around the cell membrane can be difficult to perform with 2D IR, as the bulk water dominates the final signal, it is not possible to measure the interface-specific signals. Thus, a technique with interface selectivity is essential for isolating interfacial waters and measuring specific interactions involving waters at the membrane interface. One-dimensional SFG, developed in the last 30 years, provides access to ensemble-averaged local environments at the interface, including dipole orientation, and specific hydrogen-bond networks, though heterodyne-detection needs to be incorporated to obtain an unambiguous measure of the vibrational response . The SFG method uses a narrowband visible pulse combined with a broadband IR pulse, which generates an output signal at the sum frequency of two input pulses if vibrational probes in the system resonant with the IR pulse. The output SFG pulse is mixed with a local oscillator to deconvolve the phase information. Two-dimensional vibrational sum-frequency generation (2D SFG) spectroscopy, which incorporates additional pulses to resolve dynamics, has advanced significantly over the past five years, becoming a powerful tool to investigate interfacial dynamics of membranes ( ). An IR pump pulse is implemented in SFG to provide a frequency-resolved excitation axis, similar to the pump axis in 2D IR spectroscopy. 2D SFG can be interpreted as a frequency-resolved IR "pump" and SFG "probe" technique. 2D SFG has the advantage of high selectivity towards interfacial regions with anisotropic molecular orientations, inherent to second-order nonlinear optical processes . To avoid the interference of multiple interfaces, a monolayer at the air-water interface is usually prepared (Figure ) . Using 2D SFG, the dynamics of the hydrogen-bonded and free -OH stretches of water are probed through characteristic peaks in the region of 3200 to 3700 cm -1 , providing direct access to the hydrogen bond networks of water within the first few solvation shells around the lipid headgroups. In addition, 2D SFG spectroscopy probes the picosecond spectral diffusion of the -OH stretch (Figure ). The interpretation of the lineshapes is similar to that of 2D IR spectra, where the evolution of the lineshapes provides a measure of the frequency-fluctuation correlation function of the interfacial water molecules. The time-dependent 2D SFG spectra are analyzed by the center line slope method, where different dynamics are observed for DPPG and DPTAP. In brief, the negatively charged lipid layer disrupts the water network and suppresses the fast HB dynamics due to strong hydrogen bonds involving the hydrophilic DPPG phosphatidylglycerol headgroup (Figure ). In contrast, the positively charged DPTAP layer does not have significant effects on the interfacial water ordering and dynamics, as evidenced by the fast dynamics that is comparable to bulk water . In summary, 2D SFG directly probes interfacial environments, providing a specific view of the relation between membrane composition and water dynamics. The technique can also be used to study membrane proteins , pH effects , and cation effects in the context of lipid membranes.