Pretreatment of organic samples can be achieved by removal of contaminants, or, alternatively, by isolation of sample-specific components, we discuss the molecular aspects of these two pretreatment types, together with an assessment of their effectiveness in relation to sample type. The main division in sample type is the one between carbohydrates and proteins, leading to opposite chemical strategies for the two sample categories. Recommendations for routine C-14 chemistry of organic samples also include the standardization of quality screening procedures using chemical, stable isotope and elemental data that can be collected routinely during the pretreatment of each sample.