Thin layer chromatography (TLC) has been first reported by N. A. Izmailov and M. S. Schreiber in the late 1930s. The liquid mobile phase usually moves in pores of a layer supported by a rigid plate placed vertically in a simple container, e.g., a beaker. The flow is driven by capillary forces in the pores only and no sophisticated instrumentation is required. The individual components of the mixture are separated based on differences in their affinity for the solid stationary and the liquid mobile phases. The typical format of the stationary phase represents a thin layer coated on a glass, aluminium, or plastic plate. The porous sorbents can be silicon dioxide (silica), aluminium oxide (alumina), and cellulose, held together, e.g., with gypsum. The main advantages of TLC are the ease of carrying out the separations, which can also take place in parallel lines on the same plate, simple equipment, stationary phase for single use, static detection, and the possibility of archiving the separation result in a dried layer. However, the typical 100–250 μm thick layers are not well suited for combination of TLC with mass spectrometry (MS). This has led to the commercialization of ultrathin 10 μm thick monolithic silica layers. Unfortunately, their production was soon discontinued. Alternative solutions to that problem originated from the academic environment. In one approach, the layers were formed from nanofibers prepared by electrospinning. Alternatively, the layers were porous monolithic polymers produced by polymerization in situ and a variety of separations of both small and large molecules was demonstrated. The use of MS detection then enabled determination of molecular mass of the compounds in the separated spots. Although preparation of the thin monolithic layers originally appeared straightforward, some unexpected problems had to be solved. This review details issues related to the history of the monolithic TLC and presents approaches leading to well behaving layers suitable for the desired separations.