This chapter highlights the steps that would help to analyze any fluid. It highlights importance of knowing gross analysis of fluid along with biochemical information. These parameters along with clinical information are very important in arriving at a differential diagnosis. Morphologic appearances in the fluid can often become challenging and occasionally reactive conditions can reveal changes that may mimic malignancies. This chapter provides not only a framework of approach to assessment of fluid cytology but also shows how to distinguish some of the challenging reactive conditions from the diagnosis of carcinoma. The chapter also utilizes two cases to demonstrate approach to reactive conditions. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Cytopathologic Diagnosis of Serous Fluids.