Tuning of nonlinear optical (NLO) properties of organic chromophores (OCs) by stereo-electronic and environmental effects has been widely documented by different experimental techniques and theoretical studies. Disentanglement and analysis of the different contributions requires, however, the availability of effective yet accurate quantum mechanical approaches for medium to large size systems in their natural environment. As a first step, we have shortly reviewed the phenomenological models still used by experimentalists to interpret their results and shown that a quantum mechanical approach based on the density functional theory (DFT) and the polarizable continuum model (PCM) should be able to overcome most theoretical limitations allowing, at the same time, the study of large systems with reasonable computational resources and the analysis of the results in terms of well-defined physical-chemical effects. After validation of the most suitable density functional/basis set in conjunction with the PCM description of bulk solvent effects, we have performed a systematic study of representative OCs, especially cationic ones, with special reference to their first order hyperpolarizability. The internal consistency of the results and their good agreement with experiment paves the route toward integrated experimental/computational studies of NLO properties taking together physical soundness, feasibility, reliability, and ease of interpretation.