The scientific and clinical discussion in the last few years has been focused on laser systems as an assisted method in the periodontal therapy. Objectives: The aim of this clinical and microbiological study was to investigate the influence of various lasers on the periodontal bacterial spectrum as well as changes in clinical parameters in patients with chronic periodontitis. Methods: Four methods were used to treat the periodontitis: SRP (control group), SRP + diode laser (980 nm), SRP + Nd:YAG laser (1064 nm) and SRP + photodynamic therapy (PDT, 670 nm). Ten patients were treated over a period of three months, 253 periodontal pockets were treated, 325 microbiological samples were taken and evaluated over the complete period of the study (before treatment, on the third, seventh day, one and three month after therapy). The bleeding index was measured before treatment, after one- and after three month period. The cases of periodontitis treated were assigned a treatment method randomly by quadrants as follows: one quadrant was treated with Nd:YAG laser-assisted, one with diode laser-assisted, one with PDT-assisted and one by SRP alone. Treatment was conducted with a power setting of 2 W (cw) and 75 mW in the PDT for 20 seconds irradiation. Results: Regarding bleeding on probing, the sites of the control group showed more bleeding compared laser irradiated sited after three months. The average bacterial reduction of all bacteria investigated after treatment by SRP + PDT was the best: 87.57 % (p < 0.001) on the third day and 83.74 % (p < 0.05) on the seventh day, at 80.11 % (p >0.05) after one month and 91.37 % (p > 0.05) after three month treatment period. Conclusions: This study showed that periodontal therapy assisted by PDT can present an alternative method in the initial phase of periodontal therapy.