The possible interaction and modification of cloud properties due to aerosols is one of the most poorly understood mechanisms within climate studies, resulting in the most significant uncertainty as regards radiation budgeting. In this study, we explore direct ground based remote sensing methods to assess the Aerosol-Cloud Indirect Effect directly, as space-borne retrievals are not directly suitable for simultaneous aerosol/cloud retrievals. To illustrate some of these difficulties, a statistical assessment of existing multispectral imagers on geostationary (e.g., GOES)/Moderate Resolution Imaging Spectroradiometer (MODIS) satellite retrievals of the Cloud Droplet Effective Radius (Reff) showed significant biases especially at larger solar zenith angles, further motivating the use of ground based remote sensing approaches. In particular, we discuss the potential of using a combined Microwave Radiometer (MWR)—Multi-Filter Rotating Shadowband Radiometer (MFRSR) system for real-time monitoring of Cloud Optical Depth (COD) and Cloud Droplet Effective Radius (Reff), which are combined with aerosol vertical properties from an aerosol lidar. An iterative approach combining the simultaneous observations from MFRSR and MWR are used to retrieve the COD and Reff for thick cloud cases and are extensively validated using the DoE Southern Great Plains (SGP) retrievals as well as regression based parameterized model retrievals. In addition, we account for uncertainties in background aerosol, surface albedo and the combined measurement uncertainties from the MWR and MFRSR in order to provide realistic uncertainty estimates, which is found to be ~10% for the parameter range of interest in Aerosol-Cloud Interactions. Finally, we analyze a particular case of possible aerosol-cloud interaction described in the literature at the SGP site and demonstrate that aerosol properties obtained at the surface can lead to inconclusive results in comparison to lidar-derived aerosol properties near the cloud base.