In the present study, a brief review concerning various biological activities and synthetic approaches for different phthalazine derivatives is summarized. Concerning experimental part, synthesis of the starting compounds 2-phenyl-2,3-dihydrophthalazine-1,4-dione I and 4-arylphthalazin-1(2H)-ones IIIa,b was achieved via direct condensation of phthalic anhydride with phenyl hydrazine or cyclization of the obtained 2-aroylbenzoic acids with hydrazine hydrate respectively. Alkylation of the starting materials I and IIIa,b with different chloroacetamide derivatives was done to obtain compounds Va-h and VIa-d. Also, chalcone derivatives IXa-h were obtained from alkylation of phthalazine derivative I with the 2-bromoacetanilide in acetone containing potassium carbonate. Moreover, the target 5-arylpyrazoline Xa-d and 1-acetyl-5-arylpyrazoline derivatives XIa-d were obtained via cyclization of the alkylated compounds IXa-h using hydrazine hydrate either in ethanol or acetic acid respectively. Furthermore, the hydrazide XIII was condensed with p-methoxybenzaldehyde to give the hydrazone XIV and cyclized with carbon disulfide in ethanol containing potassium hydroxide to give the oxadiazole XV. On the other hand, the hydrazones XVIIa-e, the oxadiazole derivative XVIII, the pyrazole derivative XIX and the thiosemicarbazide XX were obtained when the hydrazide XVI reacted with different aldehydes, carbon disulfide/potassium hydroxide, ethyl acetoacetate and phenylisothiocyanate respectively. Also, the thiosemicarbazide XX was cyclized to either 1,2,4-triazole-5-thione XXI or 1,3,4-thiadiazole XXII using sodium hydroxide in ethanol or concentrated sulfuric acid. Finally, the 1,2,4-triazole-5-thione XXVI and 1,3,4-thiadiazole XXVII were achieved from the thiosemicarbazide derivative XXV. Structural elucidation of the newly synthesized compounds was supported by elemental analysis, IR, 1H NMR in addition to representative 13C NMR and mass spectrometry. Anti-cancer screening of some of the newly synthesized compounds against breast cancer MCF-7 and colon cancer HCT-116 cell lines was done. Compound IXf exerted the highest cytotoxic activity against both breast cancer and colon cancer with IC50 values equal to 1.00 and 2.21 µΜ respectively Also, majority of the synthesized compounds were evaluated for their anti-microbial activity against Gram positive, Gram negative and fungal strains. Compounds XV and XVIII were the most potent showing lowest MIC against all the tested microorganisms.