Thrombocytopenia is one of the most common hematological complications of chronic liver disease (CLD) and becomes clinically relevant mainly when invasive diagnostic or therapeutic procedures are required. Its pathogenesis is multifactorial and includes splenic sequestration secondary to portal hypertension, reduced hepatic thrombopoietin (TPO) synthesis, bone marrow suppression, immune-mediated platelet destruction, and increased platelet consumption. In line with the concept of rebalanced hemostasis, platelet count alone is a poor predictor of procedural bleeding in CLD, and contemporary guidelines increasingly emphasize procedure-specific bleeding risk and patient-related factors rather than correction of an isolated laboratory value. Prophylactic platelet concentrate (PC) transfusion provides only a transient and often unpredictable platelet increment in this population and carries the risk of transfusion reactions, alloimmunization, and platelet transfusion refractoriness. This review summarizes the pathophysiology and clinical significance of thrombocytopenia in CLD, critically evaluates the indications for and efficacy of PC transfusion, and discusses alternative strategies, including recombinant human TPO, TPO receptor agonists (TPO-RAs), splenic interventions, and portal decompression. PC transfusion remains essential when rapid correction is required, particularly in active bleeding or urgent procedures, whereas the TPO-Ras, avatrombopag and lusutrombopag, offer an effective oral alternative in selected patients undergoing elective procedures. A management algorithm integrating these considerations is proposed.