The chemistry of 6-6 fused heterocycles containing three heteroatoms arranged 1:2 with no heteroatoms occupying the bridgehead position is reviewed and updated for the period 2006–18. The heterocyclic systems include those with nitrogen, oxygen, sulfur as the heteroatoms and primarily covers pyrido[x,y-z]pyridazine, pyrdimidine, pyrazine rings, along with pyrido-, pyrano-, thiopyrano[x,y-z][1,n]oxazine and thiazine rings. The reactivity, synthetic transformations and methods for their preparation, including fully conjugated and nonconjugated rings, are described. Applications of the heterocycles that have emerged in the decade include, catalytic synthetic approaches, uses in semi-conducting polymers, and significant medicinal chemistry advances (anti-cancer, anti-hypertensive and anti-pain).