To face the analysis of compounds that may be present at very low levels of concentration in complex media, such as food, environmental and biological fluids, it is possible to exploit the affinity and specificity of antibodies for their antigen by immobilizing them on a solid support. The resulting immunosorbents allow an effective extraction of compounds of interest while eliminating the other components of the matrix. The objective is then to make the analysis more reliable in terms of quantifying target analytes by eliminating matrix effects. A similar potential can also be obtained using aptamers, i.e. DNA or RNA sequences with high specificity towards compounds. The objective of this chapter is to present the respective characteristics of immunosorbents and aptamer-based sorbents, also known as oligosorbents, and their potential for the selective extraction of targeted compounds for the treatment of real samples.