I use tools to aid in the hunt for vulnerabilities, but you can't just fire off some test and assume everything is okay. When I am auditing a project I look at the code and I try and get a feel for the programmers style and skill level. If the code looks messy then chances are they are a novice and they will probably make novice mistakes.
It is important to identify security related functions in a project and manually audit them. Tamperdata is very helpful for manual auditing and exploit development because you can build custom http requests. A good example for manual auditing for PHP is: Are they using mysql_real_escape_string($var)
or are they using htmlspecialchars($var,ENT_QUOTES)
to stop sql injection? (ENT_QUOTES doesn't stop backslashes which is just as dangerous as quote marks for mysql, mssql is a different story.) Security functions are also places for "Logic errors" to crop up, and no tool is going to be able to detect this, this requires manual auditing.
If you are doing web application testing then Acunetix is the best testing tool you can use. Wapiti is a very good open source alternative. Although any tool can be used improperly. Before you do a web application test make sure error reporting is turned on, and also make sure you aren't suppressing sql errors, such as with a try/catch.
If you are doing Automated Static Code Analysis for vulnerabilities such as Buffer Overflows then Coverity is the best tool you can use(Fortify is nearly identical to Coverity). Coverity costs tens of thousands of dollars, but big names like the Department Of Homeland Security uses it. RATS is a open source alternative, although Coverity is far more complex of a tool. Both of these tools will produce a lot of false positives and false negatives. RATS looks for nasty function calls, but doesn't see if its still safe. So RATS will report every call to strcpy() strcat() sprintf(), but these can be safe if for instance you are just copying static text. This means you will have to dig though a lot of crap, but if you are doing a peer review then RATS helps a lot by narrowing the manual search. If you are trying to find a single exploitable vulnerability in a large code base, like Linux, then Rats isn't going to help much.
I have used Coverity and their sales team will claim it will "detect *ALL* vulnerabilities in your code base." But I can tell you from first hand experience that I found vanilla stack based buffer overflows with peach that Coverity didn't detect. (RATS did however pick up these issues, along with 1,000+ other function calls that where safe...) If you want a secure application or you want to find an exploitable buffer overflow then Peach is the platform tool you can use to build the tools you need.
If you are looking for more exotic memory corruption issues such as Dangling Pointers then Valgrind will help.