Monolithic columns with a unique structure possess some exceptional characteristics, which make them an excellent tool in the hands of analytical chemists, not only for separation but also for sample preparation. Their much higher external porosity compared to conventional particle-packed columns results in higher permeability and low-pressure drop with higher separation efficiency. Till now, monolithic columns have been applied to the analysis of different analytical matrices: pharmaceuticals, biofluids, food matrices, environmental samples, biochemical species, proteomics, etc. Since they offer a great potential for the separation of complex mixtures, it can be expected that the interest in applying these columns will increase. As long as more experience is gained with monolithic column technology, the emergence of applications is expected to continue. The need of reduction in organic solvent consumption also justifies this trend, in the frame of environmentally friendly methods. More and more applications using monolithic columns arise. In the future, monolithic columns are expected to prevail especially in the field of miniaturization and in chip-based nano-LC systems. In this review, we try to summarize any attempt that has been reported in the analysis of a sample of great complexity like milk using the technology of the monoliths.