Coffee is probably the main source of caffeine in human diet and, because of legal requirements and organoleptic properties, this alkaloid in this beverage is frequently quantified. This chapter presents the approaches recently developed toward this aim, focusing on different coffee sample pretreatment before detection. Main advantages and disadvantages of the described methods are briefly discussed. A new approach using low-pressure flow systems with monolithic columns has been followed in the development of new analytical methodologies. The main feature of this strategy is the compatibility of monolithic columns to traditional low-pressure flow systems, enabling chromatographic separations to be performed using current small-sized flow manifold equipment. In this context, we recently proposed a method focusing on the determination of caffeine in coffee, which is illustrated here. The experimental conditions studied and the main figures of merit obtained are presented.