Background:    Several  difficulties  remain in formulating treatment  for   chronic    hepatitis  B  (CHB), 350  million    people    are  chronically    infected   with   HBV,  Chronic  infection    with   hepatitis  B  virus   accounts   for  an   enormous   burden   of  disease  worldwide, including  up  to half   of   all   cases   of  cirrhosis, end   stage  liver  disease , and hepatocellular  carcinoma.   Aim of the work:  To maximize    the  elimination  of    the  viral  infection    while minimizing or   preventing   damage  to   the liver cells and tissues and  development of viral resistance to more antivirals.   Patients and Methods:  Eighty eight patients of chronic  hepatitis B virus infection with  resistance  to  lamivudine  treatment  as  proved   by  quantitative   PCR (more than 200 IU/ ml). Their  age  between  (20-60)  years, (85 males, and 3  females)  were  selected    from  the   National    Hepatology    and    Tropical     Medicine   Research Institute and were included in  this  study. The included  patients were two groups, the first  group  42  patients , were  receiving  Lamivudine,   plus   (Baraclude)  Entecavir (tablet 0.5mg / day)  treatment    at    the  time  of  assessment. The  second  group  46 patients    were    receiving  ( Hepsera  tablet 10 mg / day )  Adefovir   dipivoxil   plus lamivudine (tablet). All  the  patients  were  subjected  to  the  following  : thorough  history  and clinical examination, abdominal  ultrasonography  and collection of blood samples for routine liver and kidney function investigations  and  serological   assay  for HBsAg, HBsAb, HBeAg, HBeAb, HBcAb quantitative HBV DNA (PCR).   Results: Our  results  revealed   significant differences  between the  two groups of  patients  of  CHBV  infection,  resistant  to Lamivudine  drug,  the  first  group  were higher  in  response to  a  combination  between Lamivudine + (Baraclude) Entecavir, than    the   second   group   who  were  receiving  Lamivudine + (Hepsera)  Adefovir dipivoxil combination therapy.   Conclusion:  Our  study concluded  that  the clinical benefit is  apparent  with high percentage  after  a     combination   regimen  using Lamivudine  +  Entecavir  than  a combination  regimen  using  Lamivudine + Adefovir  dipivoxil  for  the treatment of resistant   chronic  hepatitis    B  virus   who   were  treated   with  Lamivudine    only before.   Recommendations: Optimal management of chronic hepatitis B,that  may  require long-term   and   sometimes   lifelong   treatment   to maintain its clinical   benefit   is challenging. It  is  important  to  initiate  treatment  with  a  drug    that  has  the  least  potential  for  induction of  drug   resistance  as  sequential  monotherapy  which  may result  in selection  of  multidrug resistant HBV mutatants.