There are only two things to worry about 1) using too much memory by loading too much data into memory

2) actual leaks (circular references) which prevent release/reuse of memory

To prevent 1) exausting memory, use a database like DBD::SQLite, DBM::Deep, BerkeleyDB...

To prevent 2) leaks, review your code for parent/child relationships, closures, circular references (self reference) , missing DESTROY/destructors, then use Scalar::Util::weaken on any duplicate references, and break circular references in destructors

bugs in HTML::TableExtract,
Tutorials: Variable Scoping in Perl: the basics,
Coping with Scoping , Mini-Tutorial: Perl's Memory Management,
Lexical scoping like a fox,
Read this if you want to cut your development time in half!,
Closure on Closures , perlref#Circular References,
Memory leaks and circular references,
Circular references and Garbage collection.,
make perl release memory,
about memory management , Re^3: Scope of lexical variables in the main script , Re: What's the weaken here for?,
Devel::Cycle,
Devel::NYTProf,
Devel::Leak Devel::LeakTrace,
WeakRef