The data on nucleophilic substitution reactions of hydrogen in 6,8‐dimethylpyrimido[4,5‐c]pyridazine‐5,7(6H,8H)‐dione, its 3‐chloride, N2‐oxide and some other derivatives are reviewed. All these compounds possess a remarkable ability to undergo not only simple functionalizations but also tandem and cascade transformations leading to annelation of various heterocyclic rings.